Current-Induced Magnetization Switching in Light-Metal-Oxide/Ferromagnetic-Metal Bilayers via Orbital Rashba Effect.

The orbital angular momentum (OAM) generation as well as its associated orbital torque is currently a matter of great interest in spin-orbitronics and is receiving increasing attention. In particular, recent theoretical work predicts that the oxidized light metal Cu can serve as an efficient OAM generator through its surface orbital Rashba effect. Here, for the first time, the crucial current-induced magnetic-field-free in-plane magnetization reversal is experimentally demonstrated in CoFeB/CuOx bilayers without any heavy elements. We show that the critical current density can be comparable to that of strong spin-orbit coupling systems with heavy metals (Pt and Ta) and that the magnetization reversal mechanism is governed by coherent rotation in the grains through the second-harmonic and magneto-optical Kerr effect measurements. Our results indicate that light metal oxides can play an equally important role as heavy metals in magnetization reversal, broadening the choice of materials for engineering spintronic devices.

γ-aminobutyric acid alleviates LPS-induced acute lung injury in mice through upregulating type B receptors.

Introduction: In recent years, studies have shown that GABA has a certain therapeutic effect on acute lung injury (ALI), but its specific mechanism has not been fully elucidated. The study was designed to investigate the protective effect and mechanism of γ-aminobutyric acid (GABA) on ALI induced by lipopolysaccharide (LPS) in mice. Material and methods: C57BL/6 mice were randomly divided into a control group, LPS group, LPS + GABA (10 mg/kg) group and LPS + dexamethasone (Dex, 5 mg/kg) group. The survival rate of each group was observed at different time points after modeling. The levels of tumor necrosis factor α (TNF-α), interleukin (IL) 1ß, 10, myeloperoxidase (MPO) and the cell count and protein concentration in bronchoalveolar lavage fluid (BALF) were measured. Lung histopathology and the expression of GABA receptors were observed by HE staining and immunohistochemistry respectively. Lung water content was assessed by wet-dry weight ratio. Results: GABA could significantly improve the survival rate and prolong the survival time of animals, alleviate the degree of inflammatory injury and pulmonary edema, reduce the content of MPO, down-regulate the levels of pro-inflammatory cytokines IL-1ß and TNF-α, and up-regulate the expression of anti-inflammatory cytokine IL-10. Moreover, GABA could significantly decrease the expression of type A receptors and enhance type B receptors. Conclusions: GABA can effectively alleviate ALI induced by LPS in mice, and its effect may be related to the upregulation of type B receptors.

Molecular mechanism of miRNA-23a in sepsis-induced lung injury.

OBJECTIVE: MicroRNA-23a-3p (miR-23a) is a novel gene regulator involved in inflammation. This study aimed to explore the molecular mechanism of miR-23a in sepsis-induced lung injury both in vitro and in vivo. METHODS: Lipopolysaccharide (LPS)- and ATP-stimulated human myeloid leukemia mononuclear cells (THP-1) and Human Bronchial Epithelial Cells (BEAS-2B) cell lines were used, while cecal ligation and puncture (CLP)-induced sepsis BABL/c mice were constructed. The mRNA expression levels of interleukin (IL)-18, IL-1ß, and miR-23a were determined, and Western blotting was used to measure CXCR4/PTEN/PI3K/AKT signaling. The concentrations of cytokines and Nod-like receptor family pyrin domain-containing 3 (NLRP3) were determined using an enzyme-linked immunosorbent assay. Lung tissue of mice was subjected to hematoxylin-eosin staining for examining myocardial injury. RESULTS: MiR-23a inhibited NLRP3 inflammasome activation in LPS- and ATP-stimulated THP-1 and BEAS-2B cells (P<0.05). Overexpression of miR-23a decreased the lactate dehydrogenase release rate in the cells (P<0.05). Meanwhile, miR-23a overexpression decreased the concentration and gene expression of IL-1ß and IL-18 in CXCR4 positive cells (P<0.05). Conversely, miR-23a knockdown increased the concentration and gene expression of IL-1ß and IL-18 (P<0.05). Additionally, PTEN and p53 proteins were up-regulated in miR-23a mimic group and down-regulated in miR-23a inhibitor group (P<0.05). Furthermore, miR-23a expression was decreased in sepsis-induced lung injury mice (P<0.05). MiR-23a overexpression reduced the sepsis-induced lung injury probably by inhibiting acetylcholinesterase activity and expression levels of IL-1ß, IL-18, capase-1, and NLRP3 (P<0.05). CONCLUSION: miR-23a can significantly alleviate sepsis-induced lung injury in CLP-induced septic mice and LPS-stimulated cell lines by suppressing NLRP3 inflammasome activation and inflammatory response, while promoting the CXCR4/PTEN/PI3K/AKT pathway.

Mechanism of miR-338-3p in sepsis-induced acute lung injury via indirectly modulating ATF4.

Sepsis is recognized as an inflammation-related syndrome in response to invading pathogens. Many patients suffer from sepsis including transplant recipients. Lipopolysaccharide (LPS) is known to trigger sepsis-related organ dysfunction. This study expounded on the possible effect of microRNA (miR)-338-3p in sepsis-induced acute lung injury (ALI). Firstly, human bronchial epithelial cell line 16HBE received LPS treatment to establish the cell models of sepsis-induced ALI. The expression patterns of miR-338-3p, long non-coding RNA OPA-interacting protein 5 antisense transcript 1 (lncRNA OIP5-AS1), and activating transcription factor 4 (ATF4) in 16HBE cells were examined. Afterwards, 16HBE cell viability, the apoptosis rate, and the levels of inflammation and lactate dehydrogenase (LDH) were determined to assess the degree of cell injury. We disclosed that LPS treatment triggered 16HBE cell injury, downregulated miR-338-3p, and upregulated OIP5-AS1 and ATF4. miR-338-3p overexpression repressed LPS-induced 16HBE cell injury. miR-338-3p diminished OIP5-AS1 stability via binding to OIP5-AS1 and downregulated OIP5-AS1 expression and OIP5-AS1 can enhance ATF4 mRNA stability and upregulate ATF4 mRNA level. The rescue experiments showed that ATF4 overexpression aggravated LPS-induced 16HBE cell injury. Overall, miR-338-3p overexpression decreased OIP5-AS1 expression and stability and further downregulated ATF4 mRNA level, thereby mitigating LPS-induced 16HBE cell injury.

Field-Free Magnetization Switching in a Ferromagnetic Single Layer through Multiple Inversion Asymmetry Engineering.

A simple, reliable, and self-switchable spin-orbit torque (SOT)-induced magnetization switching in a ferromagnetic single layer is needed for the development of next generation fully electrical controllable spintronic devices. In this work, field-free SOT-induced magnetization switching in a CoPt single layer is realized by broken multiple inversion symmetry through simultaneously introducing both oblique sputtering and a vertical composition gradient. A quantitative analysis indicates that multiple inversion asymmetries can produce dynamical bias fields along both z- and x-axes, leading to the observed field-free deterministic magnetization switching. Our study provides a method to accomplish fully electrical manipulation of magnetization in a ferromagnetic single layer without the external magnetic field and auxiliary heavy metal layer, enabling flexible design for future spin-orbit torque-based memory and logic devices.

Analysis of pathogens, drug resistance, sensitive antibiotic treatment and risk factors of early-onset sepsis in very low birth weight infants.

The clinical manifestations, types of infectious pathogens, and drug-resistant strains of sepsis in infants with very low birth weight (VLBWIs) vary greatly in different regions and hospitals. In order to improve the level of diagnosis and treatment, this study analyzed the distribution and drug resistance of the pathogenic bacteria of sepsis in VLBWIs in our hospital. A total of 69 cases of VLBWIs in Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University from January 01, 2014 to December 31, 2020 were included. Among them, 34 VLBWIs with early-onset sepsis (EOS) were assigned to the EOS group, and 14 VLBWIs with late-onset sepsis (LOS) were included in the LOS group. The distribution of pathogens and the drug resistance of antibiotics were analyzed. The results showed that fluorescent nanoparticles detected pathogenic bacteria in 48 cases, and the blood cultures were all positive. A total of 49 pathogenic bacteria were isolated, including 27 gram-negative bacteria (55.1%), 21 gram-positive bacteria (42.86%), and 1 fungus (2.04%, Candida albicans). Gram-negative bacteria comprised of E.coli and Klebsiella pneumoniae, which were highly sensitive to compound preparations containing ß-lactamase inhibitors, and carbapenem antibacterial drugs, were the first choice. Gram-positive bacteria were mainly Staphylococcus epidermidis and Streptococcus agalactiae. Staphylococcus epidermidis was highly resistant to penicillins and can be treated with vancomycin. Streptococcus agalactiae was highly resistant to penicillins and can be treated with penicillin and vancomycin. Amniotic fluid pollution, intrauterine distress, premature rupture of membranes, and maternal fever were risk factors for EOS in VLBWIs, with odds ratios (ORs) of 9.369, 6.217, 5.638, and 4.267, respectively. In summary, timely and reasonable treatment should be given based on the types and drug resistance characteristics of pathogens of neonatal sepsis and the risk factors of EOS.

Case Report: Clinical Features of a Chinese Boy With Epileptic Seizures and Intellectual Disabilities Who Carries a Truncated NUS1 Variant.

The mental retardation-55 with seizures (MRD55) is a rare genetic disease characterized by developmental delay, intellectual disability, language delay and multiple types of epileptic seizures. It is caused by pathogenic variants of the NUS1 gene, which encodes Nogo-B receptor (NgBR), a necessary subunit for the glycosylation reactions in mammals. To date, 25 disease-causing mutations of NUS1 have been reported, which are responsible for various diseases, including dystonia, Parkinson's disease, developmental and epileptic encephalopathy as well as congenital disorder of glycosylation. In addition, only 9 of these mutations were reported with detailed clinical features. There are no reports about Chinese cases with MRD55. In this study, a novel, de novo pathogenic variant of NUS1 (c.51_54delTCTG, p.L18Tfs*31) was identified in a Chinese patient with intellectual disability and epileptic seizures. This pathogenic variant resulted in truncated NgBR proteins, which might be the cause of the clinical features of the patient. Oxcarbazepine was an effective treatment for improving speech and movement of the patient, who consequently presented with no seizure. With this novel pathogenic variant found in NUS1, we expand the genotype spectrum of MRD55 and provide valuable insights into the potential genotype-phenotype correlation.

[Clinical and genetic analysis of a child with Majeed syndrome].

OBJECTIVE: To explore the clinical feature, diagnosis and phenotype of Majeed syndrome. METHODS: Clinical manifestation, diagnostic process, imaging feature and genetic testing of an ethnic Han Chinese patient with Majeed syndrome were reviewed. RESULTS: The patient, a 3-year-9-month-old boy, had featured psychomotor retardation and developed bone pain from 8 month on. The child had tenderness of the lower limbs and presented with repeatedly joint swelling and pain accompanied by fever. Physical signs included limb muscle weakening, slightly decreased muscle tone, reduced muscle volume and positive Gower sign. High-throughput sequencing revealed that the child has carried compound heterozygous variants of the LPIN2 gene, including c.1966A>G and c.2534delG. MRI showed multiple lesions in bilateral knee joints and distal middle tibia presenting as patchy SPAIR high signals with unclear edge, in addition with edema of soft tissue surrounding the right distal femur. CONCLUSION: Majeed syndrome is characterized by chronic and recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and growth retardation. Surrounding muscle tissue of osteomyelitis may also be involved. The syndrome may also affect the central nervous system, resulting in delayed language and motor development. Discovery of multiple pathological variants of the LPIN2 gene suggested that the clinical phenotype of this syndrome may vary between patients to some extent.

Long noncoding RNA differentiation antagonizing nonprotein coding RNA promotes the proliferation, invasion and migration of neuroblastoma cells via targeting ß-1, 4-galactosyltransferase III by sponging miR-338-3p.

Neuroblastoma is a common malignant tumor in children, and patients often have a poor prognosis. Long noncoding RNAs (lncRNAs) are involved in the regulation of neuroblastoma progression. However, the regulatory effect of lncRNA differentiation antagonizing nonprotein coding RNA (DANCR) on neuroblastoma is still not clear. The expression levels of DANCR, miR-338-3p and ß-1, 4-galactosyltransferase III (B4GALT3) were determined by quantitative real-time PCR. 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide, flow cytometry and transwell assays were used to evaluate the proliferation, apoptosis, migration and invasion abilities of neuroblastoma cells. Moreover, western blot analysis was performed to assess the levels of B4GALT3 and the proliferation, apoptosis and migration-related proteins. Besides, a dual-luciferase reporter assay was used to verify the interactions among DANCR, miR-338-3p and B4GALT3. Mice xenograft models were used to ascertain the effect of DANCR on neuroblastoma tumor growth in vivo. Our results revealed that DANCR was highly expressed in neuroblastoma tissues and cells, and its silencing impeded the progression of neuroblastoma cells. DANCR could interact with miR-338-3p. Knockdown of miR-338-3p recovered the inhibitory effect of DANCR knockdown on neuroblastoma progression. B4GALT3 was a target of miR-338-3p. B4GALT3 overexpression reversed the suppression effect of DANCR silencing on neuroblastoma progression. In-vivo experiments further confirmed that DANCR silencing inhibited neuroblastoma tumor growth. Our results indicated that DANCR promoted B4GALT3 expression to increase the proliferation, migration and invasion of neuroblastoma cells via sponging miR-338-3p, which provided a theoretical basis for the targeted therapy of neuroblastoma.

[Clinical and genetic analysis of a patient with Mowat-Wilson syndrome].

OBJECTIVE: To summarize the clinical phenotype and genotype of a Chinese child affected with Mowat-Wilson syndrome (MWS). METHODS: Clinical data of the patient were collected. The patient was analyzed by whole-exome sequencing (WES) as well as Sanger sequencing. RESULTS: The patient was a male infant with recurrent fever and slow growth. He also had characteristic facies, recurrent spasm, and growth retardation. WES revealed that he has carried a heterozygous nonsense c.2609C>G (p.Ser870X) variant of the ZEB2 gene (30% mosaicism). Based on the American College of Medical Genetics and Genomics standards and guidelines, the variant was predicted to be pathogenic (PVS1+PS1+PS2+PM2). CONCLUSION: The c.2609C>G variant of the ZEB2 gene probably underlay the MWS in this child. The mosaicism of the variant may explain his mild symptoms.

Organic Multiferroic Magnetoelastic Complexes.

The design of crystal structures aids the discovery of interesting physical phenomena in organic crystals. In this work, the optimization of the coronene-tetracyanoquinodimethane (TCNQ) structure generates non-degenerate energy levels of spin-up and spin-down electrons after charge transfer, producing spontaneous spin polarization, leading to pronounced ferromagnetism. The deformed crystal lattice can significantly affect the saturation magnetization of organic ferromagnets to present a remarkable magnetoelastic coupling. Furthermore, the magnetic-field-induced lattice shrinkage of the ferromagnetic crystals supports a spin-lattice-interaction-dependent magnetoelastic coupling. This concept of organic magnetoelastic coupling will pave the way for the rapid mechanical control of spin polarization in organic multiferroic magnetoelastic materials.

Distinguishing Interface Magnetoresistance and Bulk Magnetoresistance through Rectification of Schottky Heterojunctions.

High performance of many spintronic devices strongly depends on the spin-polarized electrical transport, especially the magnetoresistance (MR) in magnetic heterojunctions. However, it has been a great challenge to distinguish the bulk MR and interface MR by transport measurements because the bulk resistance and interface resistance formed a series circuit in magnetic heterojunctions. Here, a unique interface-sensitive rectification MR method is proposed to distinguish the interface MR and bulk MR of nonmagnetic In/GeO x/n-Ge and magnetic Co/GeO x/n-Ge diode-like heterojunctions. It is demonstrated that the low-field "butterfly" hysteresis loop observed only in the conventional MR curve originates from the anisotropic MR of ferromagnetic bulk Co layer, whereas the orbit-related large nonsaturating positive MR contains contributions from both the Schottky interface and bulk Ge substrate. This rectification MR method could be extended to magnetic heterojunctions with asymmetric potential barriers to realize a deeper understanding of the fundamental interface-related functionalities.

Electrically tunable tunneling rectification magnetoresistance in magnetic tunneling junctions with asymmetric barriers.

The development of multifunctional spintronic devices requires simultaneous control of multiple degrees of freedom of electrons, such as charge, spin and orbit, and especially a new physical functionality can be realized by combining two or more different physical mechanisms in one specific device. Here, we report the realization of novel tunneling rectification magnetoresistance (TRMR), where the charge-related rectification and spin-dependent tunneling magnetoresistance are integrated in Co/CoO-ZnO/Co magnetic tunneling junctions with asymmetric tunneling barriers. Moreover, by simultaneously applying direct current and alternating current to the devices, the TRMR has been remarkably tuned in the range from -300% to 2200% at low temperature. This proof-of-concept investigation provides an unexplored avenue towards electrical and magnetic control of charge and spin, which may apply to other heterojunctions to give rise to more fascinating emergent functionalities for future spintronics applications.

Room temperature electrically tunable rectification magnetoresistance in Ge-based Schottky devices.

Electrical control of magnetotransport properties is crucial for device applications in the field of spintronics. In this work, as an extension of our previous observation of rectification magnetoresistance, an innovative technique for electrical control of rectification magnetoresistance has been developed by applying direct current and alternating current simultaneously to the Ge-based Schottky devices, where the rectification magnetoresistance could be remarkably tuned in a wide range. Moreover, the interface and bulk contribution to the magnetotransport properties has been effectively separated based on the rectification magnetoresistance effect. The state-of-the-art electrical manipulation technique could be adapt to other similar heterojunctions, where fascinating rectification magnetoresistance is worthy of expectation.